ArticleThe Journal of biological chemistry2012
p63 regulates human keratinocyte proliferation via MYC-regulated gene network and differentiation commitment through cell adhesion-related gene network.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 81 citations in OpenAlex.
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- The Long Noncoding RNA PRANCR Is Associated with Alternative Splicing of Fibronectin-1 in Keratinocytes.The Journal of investigative dermatology · 2023Article
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- Skin Immunomodulation during Regeneration: Emerging New Targets.Journal of personalized medicine · 2021Review
- c-Myc Upregulated by High Glucose Inhibits HaCaT Differentiation by S100A6 Transcriptional Activation.Frontiers in endocrinology · 2021Article
- Inhibiting Hyper-O-GlcNAcylation of c-Myc accelerate diabetic wound healing by alleviating keratinocyte dysfunction.Burns & trauma · 2021Article
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- Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease.BMC medical genetics · 2020Article
- Anti-Aging Effects of GDF11 on Skin.International journal of molecular sciences · 2020Review
- Notch Signaling Pathway Expression in the Skin of Leprosy Patients: Association With Skin and Neural Damage.Frontiers in immunology · 2020Observational
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- IRF2 is a master regulator of human keratinocyte stem cell fate.Nature communications · 2019Article
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- p63 establishes epithelial enhancers at critical craniofacial development genes.Science advances · 2019Article
- ZNF185 is a p63 target gene critical for epidermal differentiation and squamous cell carcinoma development.Oncogene · 2019Article
- Wnt signaling in orofacial clefts: crosstalk, pathogenesis and models.Disease models & mechanisms · 2019Review
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although p63 and MYC are important in the control of epidermal homeostasis, the underlying molecular mechanisms governing keratinocyte proliferation or differentiation downstream of these two genes are not completely understood. By analyzing the transcriptional changes and phenotypic consequences of the loss of either p63 or MYC in human developmentally mature keratinocytes, we have characterized the networks acting downstream of these two genes to control epidermal homeostasis. We show that p63 is required to maintain growth and to commit to differentiation by two distinct mechanisms. Knockdown of p63 led to down-regulation of MYC via the Wnt/β-catenin and Notch signaling pathways and in turn reduced keratinocyte proliferation. We demonstrate that a p63-controlled keratinocyte cell fate network is essential to induce the onset of keratinocyte differentiation. This network contains several secreted proteins involved in cell migration/adhesion, including fibronectin 1 (FN1), interleukin-1β (IL1B), cysteine-rich protein 61 (CYR61), and jagged-1 (JAG1), that act downstream of p63 as key effectors to trigger differentiation. Our results characterized for the first time a connection between p63 and MYC and a cell adhesion-related network that controls differentiation. Furthermore, we show that the balance between the MYC-controlled cell cycle progression network and the p63-controlled cell adhesion-related network could dictate skin cell fate.
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